Nasal HPpSIS administration enhances NGF and tumor suppressor protein, p73 in human brain cancer tissues: preliminary data.

OBJECTIVE: Nerve Growth Factor (NGF) is a neurotrophic factor known to play a critical role in growth, survival, differentiation and neuroprotection of peripheral sensory and sympathetic neurons, as well as brain neurons. We have recently reported that nasal administration of high-pressure isotonic physiological saline solution (HPpSIS) enhances the level of NGF and the expression of NGF receptors in neurons of the olfactory bulbs and forebrain cholinergic neurons of laboratory animals. In the present study, we sought to determine whether the same treatment affects the levels of NGF within the brain tumor tissue. PATIENTS AND METHODS: This study was conducted on eight adult patients, 4 males and 4 females with malignant anterior cranial fossa tumor. Before surgery, four subjects, two males and two females received nasal administration of HPpSIS for ten consecutive days. RESULTS: The levels of NGF in surgical removed peripheral tumor brain samples of patients treated with nasal HPpSIS administration are more elevated compared to the levels of NGF in peripheral brain tissues of HPpSIS untreated patients. CONCLUSIONS: We observed that nasal administration of HPpSIS enhances not only the basal brain NGF levels and the expression of NGF receptors but also the tumor suppressor protein p73. The possible functional significance of these observations will be described and discussed.

The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor.

High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to define more clearly the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. BALB/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. HMGB1 and vascular endothelial growth factor (VEGF) were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or VEGF resulted alternatively in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF also resulted in no induction of arthritis in mice receiving exogenous HMGB1. Cytokine enzyme-linked immunosorbent assay (ELISA) analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The proinflammatory and proangiogenic cytokine IL-17A was increased when HMGB1 is inhibited, but the synovial angiogenesis was nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model.

N-Acetylcysteine and High-Dose Atorvastatin Reduce Oxidative Stress in an Ischemia-Reperfusion Model in the Rat Kidney.

OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury. METHODS: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre-ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology. RESULTS: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07). CONCLUSIONS: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering properties.

Large non-functioning parathyroid cysts: our institutional experience of a rare entity and a possible pitfall in thyroid cytology.

OBJECTIVE: Large non-functioning parathyroid cysts represent a rare entity with a benign clinical course. They may be misdiagnosed as thyroid cystic neoplasms on fine needle aspiration cytology (FNAC), resulting in inappropriate surgical treatment. We evaluated our institutional experience in the diagnosis of large parathyroid cystic lesions underlining all the differential diagnoses and pitfalls. METHODS: In the period between 1998 and 2012, we reported the cytology of eight large (>2.5 cm) parathyroid cystic lesions (all female patients) with histological control. The aspirations were performed with a 25-gauge needle with ultrasonographic guidance. The aspirated material was processed with liquid-based cytology (LBC). All the patients had normal serum parathyroid hormone (PTH) and calcium. RESULTS: The cytological samples showed a fluid watery component without colloid and few or absent epithelial cells. The resulting negativity for thyroglobulin and positivity for PTH, carried out on the cystic fluids, suggested parathyroid lesions rather than either thyroid cystic lesions (including follicular thyroid neoplasm) or cystic malignant lesions. All the patients underwent surgery without complications. CONCLUSIONS: To the best of our knowledge, this is one of the largest series with cytohistological evaluation of large parathyroid cysts. The incidence of large parathyroid cysts remains controversial as most patients are asymptomatic. FNAC may be performed with conclusive results in the majority of cystic cases. The detection of PTH and calcium on the cystic liquid is likely to achieve a correct cytological diagnosis, allowing adequate treatment and ruling out a more frequent thyroid lesion.

Haemophagocytic syndrome associated with mucormycosis infection.

Several clinical forms of mucormycosis are recognized. The tendency of mucoraceous zygomycetes to invade the blood vessels often produces a disseminated infection. A case of disseminate mucormycosis complicated by a haemophagocytic syndrome (HS) in a 32-year-old Caucasian male is reported in this article. Few cases of infection-associated HS (IAHS), involving infections caused by fungi, have been reported. In all the recorded cases, the fungal infection coexists with malignant lymphoma, immunodeficiency and a long-term steroid therapy for renal transplant or Crohn's disease. This is the second described case of the HS due to mucormycosis.

Rapamycin reduces clinical signs and neuropathic pain in a chronic model of experimental autoimmune encephalomyelitis.

Current treatments used in Multiple Sclerosis (MS) are partly effective in the early stages of the disease but display very limited benefits in patients affected by progressive MS. One possible explanation is that these therapies are unable to target the inflammatory component most active during the progressive phase of the disease, and compartmentalized behind the blood-brain barrier. Our findings show that Rapamycin ameliorates clinical and histological signs of chronic EAE when administered during ongoing disease. Moreover, Rapamycin significantly reduced the hyperalgesia observed before clinical development of EAE which, in turn, is completely abolished by the administration of the drug.

Aggressive large B-cell lymphoma in a systemic lupus erythematosus patient with chronic active Epstein-Barr virus infection: a case report.

A link between Epstein-Barr Virus (EBV) infection, systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL) has been recently reported in literature. Here we report a case of diffuse large B-cell lymphoma (DLBCL) with a particularly aggressive clinical course in an SLE patient with EBV infection. A 49-year-old woman with a long history of SLE was admitted to the Department of Experimental and Clinical Medicine and dramatically died a few hours later. The autopsy described no evidence of active lymphoproliferative disorder. Instead, histological examination demonstrated an atypical lymphocitic proliferation in lymph node, kidneys, pericardium and uterus. Immunoistochemically, the lymphomatous cells were positive with CD19, CD20, CD22 and CD79a, which was consistent with a DLBCL. The cells were also reactive to EBV markers, indicating the possible role of previous EBV infection in DLBCL pathogenesis.

Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models.

Local gene transfer of the human Lim mineralization protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. To develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP-3 and seeded on a hydroxyapatite/collagen matrix prior to autologous implantation. Here, we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing, as determined by X-rays, histology and three-dimensional microcomputed tomography (3DmuCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3 in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.